EXAM 2 Flashcards
RCT
Pro’s
- Control for all 3 biases
Con’s
- Feasible
- Generalisability due to high selectivity
- Short follow-up cannot subject people for too long
- Very control impacting the normal evolution of a disease as seen in clinical practice
When does selection bias occur?
During BOTH obtaining subjects & allocating then to the treatment or control arm.
How is selection bias minimised?
- Randomisation
- Should generate groups with similar baseline characteristics
- Block randomisation OR 1:1 randomisation - Allocation concealment (blinding)
- Allocation bias
What is performance bias?
Occurs during implementation of the intervention when either or the administrator or participant is aware which arm of the experiment they are in.
How is performance bias minimised?
Double blinding
- Blinding both the administrator and participants
- Protects against giving treatment to healthier participants
- Protects against the hawthorn affect –> participants modify their behaviour because they know they are being observed
- Protects against the placebo affect
What is attrition bias?
- Occurs during participant follow-up
- Patients who drop out are not accounted for - ADRs, motivation, forgot to record data
- Shorter trials = less bias BUT less long term affects
How is attrition bias minimised?
Attention-to-treat analysis
What is detection bias?
Measurement OR ascertainment bias
- Occurs during the evaluation of the outcome
- Data assessors know which is the control and treatment arm
How is detection bias minimised
Blinding the outcome assessors
How is risk for binary outcomes measured?
- Relative risk
- Relative risk reduction
- Relative risk increase
- Absolute risk
What is the relative risk (RR)?
Exposed event rate/control event rate
- Cross-sectional, RCTs and cohort studies
- 1 = same risk in both groups
- > 1 = exposure increases risk of the disease or treatment leads to the beneficial outcome
- <1 = exposure decreases risk of the disease
What is the relative risk reduction?
The treatment decreases your risk of the outcome by X amount
(1-RR) x 100
- Study of therapy
What is the relative risk increase?
The exposure increases your risk of the outcome by X amount
(RR-1) x 100
- Study of harm
What is the absolute risk?
> 0 increased risk of the disease outcome (ARI)
<0 decreased risk of the disease outcome (ARR)
What is the number needed to treat (NNT)?
Number of people you must treat to prevent the outcome
- SMALL number = more lives saved
1/ARR
ARR = absolute risk <0
Number needed to harm (NNH)?
Number of people that is exposed an outcome will occur.
- LARGE number = less deaths
1/ARI
ARI = absolute risk >0
How is risk for continuous outcomes measured?
Mean OR mean difference
Statistical vs clinical significance
Statistical significance is proven by the p-value and CI describing that drug A is different to drug B
Clinical significance is patient oriented based on pain scores and quality of life measures.
Superiority trial
RCT that aims to prove a new intervention is SUPERIOR to a comparator.
Inferiority trial
RCT that aims to prove an intervention is EQUAL or superior to an existing intervention.
Interim analysis
Third party analyses the data to ensure no danger is occurring to the participant.
If done early it may lead to false positives due to the lack of data at that point in time.
Cohort study
Exposed vs non-exposed cohorts are followed FORWARD in time to asses if they develop the outcome of interest.
Pro’s
- Generalisable
Con’s
- Time consuming
- Costly
- Susceptible to bias (selection, performance, attrition)
- False causation
Prospective cohort study
Participants are selected at the time the BEGIN the exposure (e.g., starting the OCP today) and then followed FORWARD in time until they develop the outcome of interest (e.g. breast cancer).
Retrospective cohort study
Participants are selected based on a PAST and CONTINUING exposure (e.g., smoked for 10 years and not gonna quite) and followed FORWARD in time until the outcome of interest is reached (e.g., lung cancer)
- Good for diseases that take time to develop as you are getting a head start on the exposure
What is the selection based on for a cohort study
Selected based on the absence or presence of an EXPOSURE and absence of the outcome
What bias is not protected for in a cohort study?
Selection & allocation bias
- It is not possible to randomise patients into groups as they know if they have the exposure or not
Performance bias
- Participants know their exposure thus cannot be blinded against this
Attrition bias
- Can be protected for BUT because of their long duration they are vulnerable to extensive drop outs
How is risk measured in a cohort study?
Relative risk
- If all the participants reach the outcome at a similar time
Person-time risk & Hazard ratios
- If participants reach the outcome at different times
What are confounders?
Prognostic variables
- Independent risk factors associated with BOTH the exposure and the outcome
- Occur due to the absence of randomisation and thus the presence of selection bias
- Corrected for via analytic correction
False causation
Occurs in observational studies (cohort and case-control) due to chance events, bias, and/or confounding variables.
False association between the exposure and outcome
Test of causation validity in observational studies
- Did the exposure precede the outcome?
- Is there a dose-dependent relationship?
- De-challenge-rechallenge strategy?
- Did other studies have the same outcome?
- Does the association make biological sense?
How are results validated in a cohort study and RCT?
- Same baseline characteristics between groups (selection bias)
- Detection methods the same (performance and measurement bias)
- Follow-up long and sufficient (attrition bias)
How is precision assessed in RCTs and cohort studies?
Confidence interval
How is the strength of an association measured in RCTs and cohort studies?
R-value
Case-control study
Participants WITH the outcome of interest (e.g. lung cancer) are surveyed about their PAST exposures to find an association between exposures and the outcome of interest.
Pro’s
- Fast
- Asses rare events (not waiting for them to happen)
Con’s
- Susceptible to bias
What is selection based on for case-control studies
Participants are selected based on having the OUTCOME or not
What biases are specific for case-control studies
Recall bias (passive) - Participants cannot remember if they had the exposure
Response bias (active) - False response because they did not want to admit their exposure
What bias is not applicable to case-control studies?
Attrition
- Participants already have the outcome
How is risk measured in case-control studies?
Odds ration (OR) - The odds of developing the disease is (OR) times greater is exposed to X >1 = harmful exposure <1 = protective exposure 1 = exposure unlikely to cause harm
Patient expected event rate (PEER)
Expected outcome rate in unexposed individuals based from general population control event rates (e.g., 10% of Australian men develop prostate cancer), other studies or extrapolated from data.
How are results validated in case-control studies?
- Cases were well defined and selected
- Information about the exposure was similarly obtained
- All confounders were accounted for
Inception study
Longitudinal study
- Cohort study whereby participants are selected near the onset of their disease
What biases are specific for prognostic studies?
Sampling bias
- Type of selection bias
- Minimised by having a detailed description of the cohort and recruiting them at similar time in their disease
Survival bias
- Occurs when the cohort was selected too late in the disease progression so that those with poor prognostic factors died prior to the study and thus were not included
- Can occur when studied are conducted in the community rather than the hospital where the really sick people are
Non-response bias
- Those who are the most sick may not respond during follow-up
- Protected for by sensitivity analysis whereby the worst and best outcomes are calculated and a range obtained
Systematic review
QUALITATIVE analysis of multiple studies.
Pro’s
- Up-to-date summary of current knowledge
- Minimal bias
- Identify gaps in knowledge
- Increased power –> combine sample sizes
- Increased precision –> multiple CI
- Rare disease and novel interventions due to combined sample sizes
- Generalisable
Con’s
- No gold standard for assessing studies
- Selective reporting of the outcomes
Publication bias
Studied with negative results are not published OR published later than positive findings.
- Occurs during article selection thus a type of selection bias AND is due to altercations in publishing so a type of reporting bias
Time lag bias
Positive results are published more rapidly
Language bias
Positive results are published in English
Multiple publication bias
Positive results are published more than once
Citation bias
Positive results are cited by others
Funnel plots
- Examine the possibility of publication bias
- Effect of the treatment is plotted against the sample size
- No bias = symmetrical funnel
- Apex represents small sample sizes with least precision
- Base represents large sample sizes with acute estimates